ArticleCancer immunology, immunotherapy : CII2006
T-cell activation and B-cell depletion in chimpanzees treated with a bispecific anti-CD19/anti-CD3 single-chain antibody construct.
Article in Cancer immunology, immunotherapy : CII, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 103 citations in OpenAlex.
- Development of VNX-101, an adeno-associated virus with less immunogenicity and efficient long-term expression of a CD19 T cell engager.Molecular therapy. Methods & clinical development · 2025Article
- Six events that shaped antibody approvals in oncology.Frontiers in immunology · 2025Review
- HPN328, a Trispecific T Cell-Activating Protein Construct Targeting DLL3-Expressing Solid Tumors.Molecular cancer therapeutics · 2024Article
- Xenograft models for pediatric cancer therapies.Faculty reviews · 2021Review
- Therapeutic Mesenchymal Stromal Cells for Immunotherapy and for Gene and Drug Delivery.Molecular therapy. Methods & clinical development · 2020Review
- Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy.Blood and lymphatic cancer : targets and therapy · 2020Review
- Pharmacokinetic Analysis of a Novel Human EGFRvIII:CD3 Bispecific Antibody in Plasma and Whole Blood Using a High-Resolution Targeted Mass Spectrometry Approach.Journal of proteome research · 2019Article
- Novel and emerging therapies for B cell lymphoma.Journal of hematology & oncology · 2019Review
- A Preclinical Population Pharmacokinetic Model for Anti-CD20/CD3 T-Cell-Dependent Bispecific Antibodies.Clinical and translational science · 2018Article
- Chimeric antigen receptor-engineered natural killer and natural killer T cells for cancer immunotherapy.Translational research : the journal of laboratory and clinical medicine · 2017Review
- Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager.Oncotarget · 2017Article
- Tetraspecific scFv construct provides NK cell mediated ADCC and self-sustaining stimuli via insertion of IL-15 as a cross-linker.Oncotarget · 2016Article
- Bispecific antibodies in cancer immunotherapy.Human vaccines & immunotherapeutics · 2016Review
- Immunotherapeutic strategies targeting natural killer T cell responses in cancer.Immunogenetics · 2016Review
- Novel immunotherapies in lymphoid malignancies.Nature reviews. Clinical oncology · 2016Review
- CD19xCD3 DART protein mediates human B-cell depletion in vivo in humanized BLT mice.Molecular therapy oncolytics · 2016Article
- Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward?Antibodies (Basel, Switzerland) · 2015Review
- Bispecific antibody releasing-mesenchymal stromal cell machinery for retargeting T cells towards acute myeloid leukemia blasts.Blood cancer journal · 2015Article
- Bispecific T-cell engagers for cancer immunotherapy.Immunology and cell biology · 2015Review
- AntiCD3Fv fused to human interleukin-3 deletion variant redirected T cells against human acute myeloid leukemic stem cells.Journal of hematology & oncology · 2015Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BscCD19xCD3 is a bispecific single-chain antibody construct with exceptional cytotoxic potency in vitro and in vivo. Here, we have investigated the biological activity of bscCD19xCD3 in chimpanzee, the only animal species identified in which bscCD19xCD3 showed bispecific binding, redirected B-cell lysis and cytokine production comparable to human cells. Pharmacokinetic analysis following 2-h intravenous infusion of 0.06, 0.1 or 0.12 mug/kg of bscCD19xCD3 as part of a dose escalation study in a single female chimpanzee revealed a half-life of approximately 2 h and elimination of the bispecific antibody from circulation within approximately 8 h after the end of infusion. This short exposure to bscCD19xCD3 elicited a transient increase in serum levels of IFNgamma, IL-6, IL-2, soluble CD25, and transiently upregulated expression of CD69 and MHC class II on CD8-positive cells. Cytokine release and upregulation of T-cell activation markers were not observed with vehicle controls. A multiple-dose study using 5 weekly doses of 0.1 mug/kg in two animals also showed transient cytokine release and an activation of peripheral T cells with a first-dose effect, accompanied by a transient lymphopenia. While oscillations of T-cell counts were relatively even during repeated treatments, the amplitudes of peripheral B cells declined with every infusion, which was not observed in a vehicle control animal. Our data show that bscCD19xCD3 can be safely administered to chimpanzees at dose levels that cause fully reversible T-cell activation and, despite a very short exposure time, cumulative loss of peripheral B lymphocytes. A clinical trial testing prolonged administration of bscCD19xCD3 (MT103) for improving efficacy is currently ongoing.
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Registered trials
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